Isoxazole fungicidal compositions and methods of use

ABSTRACT

AGRICULTURAL FUNGICIDAL COMPOSITIONS WHICH COMPRISE A FUNGICIDALLY EFFECTIVE AMOUNT OF AN ISOXAZOLE DERIVATIVE HAVING THE FORMULA   3-(R3-COO-),4-R1,5-R2-ISOXAZOLE   WHEREIN R1 IS HYDROGEN ATOM, A HALOGEN ATOM OR AN ALKYL GROUP OF 1 TO 3 CARBON ATOMS; R2 IS HYDROGEN ATOM OR AN ALKYL GROUP OF 1 TO 3 CARBON ATOMS; AND R3 IS AN ALKOXY GROUP OF 1 TO 5 CARBON ATOMS OR AN ARYL GROUP WHICH CONTAINS 6 TO 10 CARBON ATOMS, THE HYDROGEN ATOM ON ONE OF MORE RING CARBONS OF WHICH MAY BE SUBSTITUTED WITH ALKYL OF 1 TO 5 CARBON ATOMS, ALKOXY OF 1 TO 3 CARBON ATOMS, NITRO, HALOGEN OR METHYLENEDIOXY, AND AN AGRICULTURALLY-ACCEPTABLE CARRIER. THE PRESENT FUNGICIDAL COMPOSITION CAN BE UTILIZED FOR COMBATTING A WIDE RANGE OF PATHOGENIC FUNGI CAUSING PLANT DISEASES, ESPECIALLY THOSE CAUSED BY VARIOUS PATHOGENIC FUNGI BELONGING TO THE GENERA FUSARIUM, PYTHIUM, RHIZOCTONIA, PHYTOPHTHORA AND THE LIKE.

United States Patent Int. (21. A011; 9/22, 9/28 US. Cl. 424-272 4 ClaimsABSTRACT OF THE DISCLOSURE Agricultural fungicidal compositions whichcomprise a fungicidally effective amount of an isoxazole derivativehaving the formula wherein R is hydrogen atom, a halogen atom or analkyl group of l to 3 carbon atoms; R, is hydrogen atom or an alkylgroup of 1 to 3 carbon atoms; and R is an alkoxy group of l to carbonatoms or an aryl group which contains 6 to carbon atoms, the hydrogenatom on one of more ring carbons of which may be substituted with alkylof 1 to 5 carbon atoms, alkoxy of 1 to 3 carbon atoms, nitro, halogen ormethylenedioxy, and an agriculturally-acceptable carrier. The presentfungicidal composition can be utilized for combatting a wide range ofpathogenic fungi causing plant diseases, especially those caused byvarious pathogenic fungi belonging to the genera Fusarium, Pythium,Rhizoctonia, Phytophthora and the like.

This invention relates to an agricultural fungicidal composition and amethod for combatting various pathogenic fungi causing plant diseases.

More particularly, it relates to an agricultural fungicidal compositionwhich comprises a fungicidally effective amount of an isoxazolederivative having the formula R1 lL B wherein R is hydrogen atom, ahalogen atom or an alkyl group of 1 to 3 carbon atoms, R is hydrogenatom or an alkyl group of 1 to 3 carbon atoms and R is an alkoxy groupof 1 to 5 carbon atoms or an aryl group which contains 6 to 10 carbonatoms, the hydrogen atom on one or more ring carbon atoms of which maybe substituted with alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 3carbon atoms, nitro, halogen or methylenedioxy, and afungicidally-acceptable carrier. It also relates to a method forcombatting pathogenic fungi which comprises treating the infested plantsor the plant to be protected with a fungicidally effective amount of theabovementioned isoxazole derivative (I).

In the above Formula I, the group R may be illustrated by hydrogen,methyl, ethyl, n-propyl, i-propyl, chlorine, bromine, fluorine oriodine, the group R may be illustrated by hydrogen, methyl, ethyl,n-propyl or i-propyl and the group R may be illustrated by methoxy,ethoxy, n-propoxy, i-propoxy, n-butoxy, tert.-butoxy, n-pentoxy, phenyl,naphthyl, o-, mor p-tolyl, 0-, mor 3,629,430 Patented Dec. 21, 1971 haswherein R is hydrogen, an alkyl group, a dialkoxymethyl group of 1 to 5carbon atoms are eifective for combatting certain types of soil-bornepathogenic fungi.

However, such prior fungicidal isoxazoles are found to have somedisadvantages of showing fungicidal activity against only limited typesof soil-borne diseases, especially those caused by Fusarium and Pythiumfungi and of being not so much effective against other soilbornepathogenic fungi such as those belonging to the genera Rhizoctonia andPhytophthora and also of not showing satisfactorily fungicidal activityagainst various pathogenic fungi which will attack the ground parts ofplants.

Now, as a result of our further extensive investigations on fungicidalactivity of many isoxazole derivatives, it has been unexpectedly foundthat the isoxazole derivatives of the above Formula I exhibit morepotent fungicidal activity against not only soil-borne pathogenic fungibelonging to the genera Fusarium and Phythium but also those fungibelonging to the genera Rhizoctonia and Phytophthora, without any degreeof phytotoxicity even if applied in a considerably large amount, andthey also show excellent and durable fungicidal activity as foliarfungicide for the treatment and prevention of a wide range of plantdiseases with favourable growth promoting action on the host plant, ascompared with the abovementioned prior fungicidal isoxazole derivatives.

It is accordingly an object of this invention to provide an agriculturalfungicidal composition which comprises a fungicidally effective amountof the isoxazole of the above Formula I and an agriculturally-acceptablecarrier.

It is another object of this invention to provide a. method forcombatting pathogenic fungi which comprises treating the infested plantsor the plants to be protected with a fungicidally effective amount ofthe isoxazole derivative of the above Formula I.

These and other objects of this invention will be apparent from thefollowing detailed description of this invention.

The isoxazole derivatives of the above Formula I are all novel compoundsunknown in the prior art. These novel isoxazole compounds (I) can beeasily prepared by reacting a 3-hydroxyisoxazole derivative having theformula (III) wherein R and R are as defined above with an acid halidehaving the formula wherein R is as defined above and X is chlorine orbromine, if necessary in the presence of an acid binding agent, e.g.caustic alkali, a tertiary amine and the like.

Representative examples of the active isoxazole derivatives (I) employedin this invention and some embodiments of the preparation of saidisoxazole derivatives are given hereinbelow only for the purpose ofillustration.

(1) 3-benzoyloxy-5-methylisoxazo1e (M.P. 39 C.);

(2) 3-(4-methylbenzoyloxy) methylisoxazole (M.P.

(3) 3 (2 methylbenzoyloxy)-5-methylisoxazole (M.P.

(4) 3 (3 methylbenzoyloxy)-5-methylisoxazole (B.P.

155-160 C./0.9 mm. Hg);

(5) 3 (4 nitrobenzoyloxy) S-methylisoxazole (M.P.

(6) 3 (2,4 dichlorobenzoyloxy) S-methylisoxazole M.P. 74-75 C.);

(7) 3 (3 methylbenzoyloxy)-4-chloro-5-methylisoxazole (M.P. 63.565 C.);

(8) 3 (4 methoxybenzoyloxy) S-methylisoxazole (M.P. 85.5-86.5 C.);

(9) 3-(2 methylbenzoyloxy)isoxazole (B.P. 135-140 C./0.9 mm. Hg);

(10) 3 (4 tert.-buty1benzoyloxy) S-methylisoxazole,

(M.P. 85.5-86.5 C.);

(11) 3 (2,3 dimethoxybenzoyloxy)-5-methylisoxazole (M.P. 63.5-65.5 C.);

(12) 3 (3,4-methylenedioxybenzoyloxy)-5-methylisoxazole (M.P. 1l7.5 C.);

(13) 3 (2 methylbenzoyloxy) 4,5-dimethylisoxazole (B.P. 140l50 C./0.3mm. Hg);

(14) 3 (2,3,4,5,6 pentachlorobenzoyloxy) S-methylisoxazole (M.P. 128-129C.);

( 15) 3 ethoxycarbonyloxyisoxazole (B.P. 85-90 C./

0.4 mm. Hg);

(16) 3 isobutoxycarbonyloxy 5 methylisoxazole (B.P.

146149 C./0.3 mm. Hg);

(17) 3 methoxycarbonyloxy S-methylisoxazole (B.P.

110-115 C./3 mm. Hg);

(18) 3 ethoxycarbonyloxy 4,5-dimethylisoxazole (B.P.

130 C./0.45 mm. Hg);

(19) 3 ethoxycarbonyloxy-S-methylisoxazole (B.P. 125- 130 C./3 mm. Hg);

(20) 3 8 naphthoyloxy-S-methylisoxazole (M.P. 74.5-

(21) 3 a naphthoyloxy S-methylisoxazole (M.P. 88-

(22) 3 (4 chlorobenzoyloxy)-5-methylisoxazole (M.P.

9698 C.); and

(23) 3 (2 chlorobenzoyloxy)-5-methylisoxazole (M.P.

PREPARATION A 3-benzoyloxy-S-methylisoxazole To a solution of 4.95 g. of3-hydroxy-5-methylisoxazole in ml. of pyridine was added dropwise underice cooling a solution of 7.0 g. of benzoyl chloride in 30 ml. ofpyridine. After completion of the dropwise addition, the reactionmixture was allowed to rise to room temperature and stirred at thattemperature for 2 hours. Then, the whole reaction mixture was pouredinto 600 ml. of a cooled aqueous hydrochloric acid solution. Theresulting mixture was extracted into benzene and the extract was washedsuccessively with 3% aqueous hydrochloric acid, water, 3% aqueous sodiumbicarbonate and then saturated aqueous sodium chloride and dried overanhydrous sodium sulfate. Then, the benzene was distilled off underreduced pressure and the residue was recrystallized from n-hexane togive the title compound as colorless needles melting at 38-39 C.

4 PREPARATION B 3- (4-methoxybenzoyloxy) -5-methylisoxazole To asuspension of 1.2 g. of sodium salt of 3-hydroxy- S-methylisoxazole in30 ml. of acetonitrile was added dropwise with stirring and cooling asolution of 1.0 g. of p-methoxybenzoyl chloride in 10 ml. ofacetonitrile. After completion of the dropwise addition, the resultingmixture was allowed to stand overnight at room temperature, theinsoluble substance which precipitated in situ was removed by filtrationand washed with benzene. The filtrate and the washings were combined andthe solvent was distilled off under reduced pressure. The residue wasrecrystallized from n-hexane to give the title compound as colorlesscrystals melting at 85.5-86.5 C.

The active compound (I) used in the fungicidal composition according tothis invention may be conveniently formulated by known procedures andused in various forms including liquids, dusts, granules and wettablepowders etc.

Liquids may be prepared by dissolving the active compound in anagriculturally-acceptable liquid carrier, i.e. a suitable solvent withor without one or more of known adjuvants commonly employed in the artsuch as emulsifying agents, wetting agents, or dispersing agents.Suitable solvents include water, alcohols such as methanol or ethanol,acetone, benzene, toluene, xylenes, solvent naphtha, petroleum ether,the mixture thereof and the like. Suitable adjuvants may be any of thosewhich is ordinarily employed in the art, and include, for example, thecondensation products of alkylene oxides with phenols or organic acids,alkylarylsulfonates, dialkyl sulfosuccinate, polyoxyethylene ether orester derivatives of alcohols or acids and the like.

Dusts and granules may be prepared by mixing said active compound in andon an inert agriculturally-acceptable solid carrier by a conventionalprocedure. Suitable solid carriers for use in the composition of thisinvention include, for example, talc, pyrophylite, kieselguhr, clay,bentonite, diatomaceous earth, kaolin, precipitated chalk and the like.

Wettable powders may be prepared by mixing the said active compound withone or more of the aforementioned solid carriers and suitable dispersingagents. Suitable dispersing agents include, for examples, thoseaforementioned adjuvants such as alkylbenzenesulfonates, lignosulfonatesor polyoxyalkylene glycol ethers or esters.

The concentration of the active compound in the composition of thisinvention may normally be from about 0.1 to about 95% by weight, andpreferably from about 0.5 to about by weight, based upon the totalweight of the composition, although the amount of the active ingredientemployed will largely depend upon such factors as the type and severityof diseases, the form of a composition or the specific active compound.It should be, however, understood that the amount of an active compoundemployed is to be not a critical feature of this invention. Two or moreof said active ingredients may be conveniently incorporated into theagricultural fungicidal composition of this invention.

The agricultural fungicidal composition of this invention may alsoinclude other known fungicidal agents e.g. pentachloronitrobenzene,tetramethylthiuram disulfide, dimethylaminobenzene diazo sodiumsulfonate, N-trichloromethylthio 4 cyclohexane 1,2 dicarboxyimide,trichloro-Z-nitropropane, 5-ethoXy-3-trichloromethyl 1,2,4- thiadiazoleand the like; insecticidal agents, e.g. l,4,5,6, 7,8,8-heptachloro 3a4,7,7a-tetrahydro-4,7-methanoindene, benzenehexachloride,l,l,l-trichloro-2,2-bis(p-chlorophenyl)ethane, 0,0-dimethylS-(N-methylcarbamoylmethyl)phosphorodithioate, 0,0-diethylS-Z-(ethylthio) ethyl phosphorodithioate and the like; fertilizers, andthe like.

In order to illustrate the excellent fungicidal activity of the activeisoxazole derivative (I) according to this in vention, the comparativetestings and the results thereof are given hereinbelow:

EXPERIMENT 1 Test for preventive and curative eifects of the activeisoxazole derivative according to this invention against soft rot inkidney beans Method and material.As a host plant were employed youngkidney bean seedlings which had been previously grown on a nursery in agreenhouse. For each test run were used two test spots, each containingabout 30 growing seedlings. Host plants were inoculated with Sclerotiniasclerotiorum, which had been incubated at 28 C. for about 2 weeks in alaboratory, by admixing an adequate amount of said pathogenic funguswith a suitable amount of shallow surface soil. On 2nd and 10th daysafter inoculation with the pathogenic fungus, the test compound asindicated hereinbelow was applied to the host spot in the form of aliquid preparation in an amount of 100 1./10 a., respectively.

The above liquid preparation was made by mixing and pulverizing the testcompound 50% by weight, a mixture of clay and diatomaceous earth (1:1)47% by weight and polyoxyethylene nonylphenyl ether 1% by weight,diluting the resulting wettable powder with water to a preparationhaving the concentration as given hereinbelow and then adding to thediluted preparation 0.03% by weight of a spreader [Gramin (registeredtrade name), a mixture of polyoxyethylene dodecyl ether, polyoxyethylenearyl ether sulfonic acid and abietic acid polyalcohol ester manufacturedand sold by Sankyo Company Ltd., Japan].

After 20 days of the inoculation, host plants were visually observed,both killed plant and plant with a browncolored stern were rated asdiseased and then the average percentage of diseased rating wascalculated, based upon the number of the diseased plants in two spots.

Results.-The results are summarized in the following Table I.

TABLE I Concentration the test compound in the Diseased liquidprepararating Phyto- Test compound tion(' /m1.) (percent) tox1c1tyControl (3-hydroxy-5-meti1yl- 1,000 26.5 isoxazole). 300 68.7

Non-treated 79.3

1 Test compound is indicated by means of the number as given to theisoxazole derivatives listed hereinabove, [or convenience andimplification.

EXPERIMENT 2 Test for preventive and curative effect of the activeisoxazole derivative according to this invention against tomato lateblight Method and material-The test compound as indicated hereinbelowwas applied to tomatoes with 5-6 leave period by spraying as a liquidpreparation made as in the above Experiment 1 in an amount of 40 ml. fortwo test pots containing said growing host plants. After air-drying,host plants were inoculated by spraying with spores of potato lateblight (Phy,t0phth0ra infestans). The inoculated host plants were placedfor 24 hours in a room maintained at 20 C. and at a relative humidity ofabove and then removed into a greenhouse at 25 C. After 5 days, totalarea of the lesions in upper three leaves was measured and then averagearea of the lesion per leaf was calculated.

Results.-The results are summarized in the following Table "II.

TABLE II Concentration the test Average compound in area of the liquidpreplesion Phyto- Test 1 compound aratlon ('y/ml.) (percent) toxicityControl (3-hydroxy-5-methyi- 1,000 59.3 isoxazole). 300 83.4

Non-treated 100.0

1 Of. the footnote in the above Table I.

EXPERIMENT 3 Test for preventive and curative effects against soilbomediseases Method and material.-The following pathogenic fungi, which hadbeen previously cultivated in bran at 28 C. for 2 weeks, were uniformlyadmixed with a separate portion of test soil, respectively.

Rhizoctonia vagum, Fusarium oxysporum, and Pythium aphanidermatum.

TABLE III TABLE V Fungicidal effect against Rhizoctom'a vagum Fungioidalefiect against Pythium aphanidermatum Number i killed Number of KilledDose seedlings after seeding Does seedlings after seeding rate PhytoratePhyto- Test compound (g./l0 a.) 10th day 20th day toxicity Test eompound(g./a.) 10th day 20th day toxicity Control (3-hydroxy-5- 3,000 18 36Control 3-hydroxy-5- methylisoxazole). 1,000 32 69 methylrsoxazole)- 21% 300 50 93 35 300 24 41 Non-treated 100 120 Non-treated 96 110 1 Of.the footnote in the above Table I. of th f t t th b T b1 I TABLE IV 6 00no. 0 111 e a 0V0 El e Fungicidal efieot against Fusariu'm ozysporum 40The followmg examples are glven P1113 for the P P of illustrating somepreferred embodiments of the agricul- Number of killed D Seedlings afterseeding tural fungicldal composltions and methods for combatting ratePhyto- Test 1 compound (El/ma.) 10th day 20th day toxicity pathogemciungi according to thls mvennon. All parts are given by weight. I 13,000 0 0 1,000 0 1 EXAMPLE 1 300 1 8 Dust 3 3,000 0 0 Th f u 1 d 1,0000 0 e o owing 1ngred1ents were uni orrny mixed an 300 0 2 pulverlzed tomake a dust.

1,000 3 5 I Paits 300 7 13 3-benz0y10xy-S-methylrsoxazole 5 Clay-talc(1:1) 94 8 3,000 0 0 1,000 0 2 Red 1ron oxide 0.5 300 3 5 Whitecarbon0.5

9 $33: 8 g I The dust thus made was plowed into soil in sugar beet 300 26 or vegetable fields at the dose rate of 10 kg./l0 a. before 11 3,000 00 seeding or planting for the preventive and curative treatbggg 3 meritof damping-off.

. I 13 3,000 0 0 ()0 EXAMPLE 2 288 g Emulsifiable concentrate 8 g Thefollowing ingredients were throughly mixed to 1 4 I make anernulsifiable concentrate.

1,000 0 1 Parts 300 0 5 3-(4-rnethylbenzoyloxy)-5-methylisoxaz0le 30 gAcetone-benzene-ethanol 63 1 3 I Newcol (registered trademark of anemulsifying 21 3,000 0 2 agent manufactured and sold by Nihcn Nyukazai300 5 15 10 pan) 7 38 i i-g ggigf @883 3 i The emulsifiable concentratethus made was diluted y 12 51 I with 500-1000 times volume of water andapplied to sugar Non-treated 4 117 beets, vegetables or rice by pouringin each trench at 1 2 r 1CLthefootnotemtheaboveTubleL rates of 2 3l./rn. before seeding or planting for the preventive and curativetreatment of damping-01f.

The emulsifiable concentrate was also diluted with 500- 1000 timesvolume of water and applied to crops by pouring in the part near theroot thereof at rates of 2-3 l./m, at intervals of 7-10 days during thegrowing period.

EXAMPLE 3 Wettable powder The following ingredients were uniformly mixedand pulverized to make a wettable powder.

Parts 3-(S-methylbenzoyloxy)-5-methylisoxazole 50 Clay-diatomaceousearth (1:1) 47 Polyoxyethylene nonylphenyl ether 2 Polyvinyl alcohol 1The wettable powder thus made was diluted with 500- 1000 times volume ofwater and applied to sugar beets or vegetable for the preventive andcurative treatment of damping-off and to cucumber melons and gourdfamily for Fusarium wilt by pouring in each trench or the part near theroot at rates of 2-3 l./m. during the growing period or before and afterseeding or planting.

The wettable powder was also diluted with 1000-2000 times volume ofwater and applied to kidney beans by spraying at rates of 100 l./l a.for the preventive and curative treatment of soft rot.

What is claimed is:

1. An agricultural fungicidal composition which comprises a fungicidallyeifective amount of a compound having the formula R; L H R wherein R ishydrogen, halogen or alkyl of 1 to 3 carbon atoms, R is hydrogen oralkyl of 1 to 3 carbon atoms and R is alkoxy of 1 to carbon atoms,phenyl, naphthyl, 0-, m-, or p-tolyl, 0-, mor p-nitrophenyl, 0-, morpchlorophenyl, o-, mor p-tert.-butylphenyl, 0-, mor ptert.-butoxyphenyl,p-methoxyphenyl, 2,4-dichlorophenyl, 2,3,4,5,6-pentadhlorophenyl,2,3-dimethoxyphenyl, or 3,4- methylenedioxphenyl, and anagriculturally-acceptable carrier, said fungicidally effective amountbeing about 05-70% by weight, based upon the total weight of thecomposition.

2. The composition according to claim 1 wherein said compound isselected from the group consisting of O oil-R,

3- (Z-methylbenzoyloxy) -5-methylisoxazole,3-(3-methylbenzoyloxy)-5-methylisoxazole, 3 (4-methylbenzoyloxy -5-methylisoxazole,

3-(4-methoxybenzoyloxy)-5-methylisoxazole, 3- 4-tert.-butylbenzoyloxy-5-methylisoxazole, 3- 2,3-dimethoxybenzoyloxy) -5-methylisoxazole, 3-(3 ,4-methylenedioxybenzoyloxy) -5-methylisoxazole,3-isobutoxycarbonyloxy-S-methylisoxazole,3-rnethoxycarbonyloxy-S-methylisoxazole and3-ethoxycarbonyloxy-S-methylisoxazole.

3. A method for combatting pathogenic fungi which comprises treatingsaid fungi with a fungicidally elfective amount of a compound having theformula wherein R is hydrogen, halogen or alkyl of 1 to 3 carbon atoms,R is hydrogen or alkyl of 1 to 3 carbon atoms and R is alkoxy of 1 to 5carbon atoms, phenyl, naphthyl, o-, mor p-tolyl, o-, mor p-nitrophenyl,o-, mor pchlorophenyl, o-, mor p-tert.-butylphenyl, o-, morptert.-butoxyphenyl, p-methoxyphenyl, 2,4-dichlorophenyl,2,3,4,5,6-pentachlorophenyl, 2,3-dimethoxyphenyl, or 3,4-methylenedioxphenyl.

4. The method according to claim 3 wherein said compound is selectedfrom the group consisting of 3-(Z-methylbenzoyloxy)-5-rnethylisoxazole,3-(3-methylbenzoyl0xy)-5-methylisoXaZole,3-(4-methylbenzoyloxy)-5-methylisoxazole,3-(4-methoxybenzoy1oxy)-5-methylisoxazole,

3 (4-tert.-butylbenzoyloxy) -5-methylisoxazole,3-(2,3-dimethoxybenzoyloxy)-5-methylisoxazole,3-(3,4-methylenedioxybenzoyloxy)-5-methylisoxazole,3-isobutoxycarbonyloxy-5-methylisoxazole,3-methoxycarbonyloxy-S-methylisoxazole and3-ethoxycarbonyloxy-S-methylisoxazole.

References Cited UNITED STATES PATENTS 3,207,76l 9/1965 Bay 4242723,366,537 1/1968 Woolf 424-272 3,410,860 11/1968 Haber et a1 424272FOREIGN PATENTS 1,446,728 6/ 1966 France 424-272 ALBERT T. MEY'ERS,Primary Examiner 0 N. A. DREZIN, Assistant Examiner US. Cl. X.'R.

